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P751 DISTINCT VALUES OF LIVER STIFFNESS PREDICT PROGRESSION TO ADVANCED LIVER FIBROSIS IN HIV-INFECTED PATIENTS WITH CHRONIC HEPATITIS C
POSTERS fibrosis (<8 kPa), 19% moderate fibrosis (8–12.3 kPa) and 15% severe fibrosis/cirrhosis (>12.3 kPa). Beyond HCV, important correlates of cirrhosis included BMI, HBsAg+, alcohol, IR and steatosis (table). Table: Factors independently associated with cirrhosis (Liver stiffness >12.3 kPa; n = 696)
Age (per 5 years) Body mass index (per 2 kg/m2 ) Hepatitis C virus Negative HCV RNA <2.8 log10 IU/ml HCV RNA 2.8–5 log10 IU/ml HCV RNA 5–6 log10 IU/ml HCV RNA >6 log10 IU/ml HIV Negative HIV RNA undetectable HIV RNA 1.6–4.0 log10 IU/ml HIV RNA >4.0 log10 IU/ml Hepatitis B Surface Antigen positive Insulin Resistance (HOMA-IR) HDL cholesterol (mg/dl) LDL cholesterol (mg/dl) Triglycerides (mg/dl) Alcohol dependence None Harmful drinking Hazardous drinking/dependence Steatosis None Mild Moderate
Prevalence (%), Median (IQR)
Prevalence ratio of cirrhosis (95% confidence interval)
40 (34, 45) 20 (18, 23)
1.18 (1.06, 1.31)* 1.11 (1.03, 1.21)*
383 (56) 65 (10) 12 (2) 48 (7) 174 (26)
1 2.01 (1.09, 3.69)* 1.92 (0.68, 5.40) 3.89 (2.34, 6.49)* 4.26 (2.74, 6.61)*
560 (81) 33 (5) 35 (5) 62 (9) 58 (8) 1.23 (0.55, 2.44) 40 (32, 53) 98 (76, 123) 90 (67, 128)
1 0.44 (0.11, 1.77) 0.75 (0.34, 1.67) 1.10 (0.65, 1.87) 2.12 (1.23, 3.65)* 1.06 (1.02, 1.10)*
144 (21) 86 (12) 466 (67)
1 1.33 (0.69, 2.55) 1.68 (1.03, 2.74)*
341 (49) 290 (42) 58 (8)
1 1.30 (0.91, 1.87) 2.60 (1.54, 4.39)*
*Statistically significant.
Conclusions: In this Indian cohort, beyond HCV, liver fibrosis was driven by alcohol use and metabolic parameters including IR and steatosis. As advances in HCV treatment continue, efforts need to expand access in LMICs and need to consider the increased prevalence of IR and steatosis which may impact disease progression and treatment response. P750 SPONTANEOUS HCV CLEARANCE IN HIV PATIENTS WITH CHRONIC HEPATITIS C BEARING FAVORABLE IL28B ALLELES ON ANTIRETROVIRAL THERAPY E. Vispo, P. Barreiro, J.V. Fernandez-Montero, P. Labarga, C. de Mendoza, A. Trevino, ˜ V. Soriano. Infectious Diseases, Hospital Carlos III, Madrid, Spain E-mail: [email protected] Background and Aims: A quarter of individuals acutely infected with HCV clear the virus spontaneously. Female gender, symptomatic acute hepatitis and IL28B-CC alleles predict a selflimited course. Once chronic HCV infection is established, viral elimination can only be achieved using specific antiviral therapy. Herein, we report a group of chronically HIV–HCV coinfected patients that cleared HCV spontaneously while receiving only antiretrovirals. Methods: Retrospective analysis of all HIV+ individuals with positive HCV-antibodies (HCV-Ab) and negative serum HCV-RNA attended during year 2012 at a reference HIV clinic in Madrid. Results: From a total of 2366 HIV+ individuals, 618 (26%) were HCV-Ab+, of whom 387 (62%) were also positive for serum HCV-RNA. Individuals HCV-Ab+/HCV-RNA-negative were grouped into two categories, those that had eliminated the virus following a course of antiviral treatment (n = 198; 86%) and those who had cleared the virus spontaneously (n = 33; 14%). Eight of the latter were positive for HBsAg and might have cleared HCV as result of
viral interference. However, 6 (24%) out of the remaining 25 did so after being positive for serum HCV-RNA >6 months (median 3.6 years, range 16–120 months). All harbored IL28B-CC alleles and had undetectable plasma HIV-RNA on HAART around the time of HCV clearance. Conclusions: Spontaneous HCV clearance may occur in a subset of chronically HIV/HCV-coinfected patients harboring IL28B-CC whereas being on HAART. Given that antiretrovirals do not display any direct anti-HCV activity, recovery of innate immune responses could be responsible for these late HCV clearance episodes. Thus, periodic testing of serum HCV-RNA is warranted in chronically HIV/HCV-coinfected patients on HAART. P751 DISTINCT VALUES OF LIVER STIFFNESS PREDICT PROGRESSION TO ADVANCED LIVER FIBROSIS IN HIV-INFECTED PATIENTS WITH CHRONIC HEPATITIS C P. Labarga, J.V. Fernandez-Montero, P. Barreiro, M.E. Vispo, R. Sierra, I. Perez, C. de Mendoza, V. Soriano. Hospital Carlos III, Madrid, Spain E-mail: [email protected] Background and Aims: The use of DAA is restricted by some governments to patients with advanced liver fibrosis in order to save costs. However, response rates are lower in patients with advanced liver fibrosis. Methods: All HCV/HIV-confected patients with Metavir F0–F2 (liver stiffness <9.6 kPa by elastometry), and with a follow-up >3 years were identified at our institution. Liver fibrosis progression (LFP) was defined as a change to Metavir F3–F4 estimates. Results: A total of 344 HIV/HCV-coinfected patients with baseline F0–F2 were identified. Hepatitis C therapy was given to 205, of whom 94 (44.8%) achieved SVR. Significant differences between groups included a lower proportion of genotypes 1–4 vs 2–3 (52% vs 90% p < 0.001) and higher IL28B-CC vs non-CC (63% vs 25%, p < 0.001) among SVR patients. After 53 months mean followup, LFP occurred in 5.4% SVR, 25.7% non-SVR and 18% nottreated patients (p = 0.005 SVR vs others). In multivariate analysis, only achievement of SVR independently prevented from LFP (OR 0.47 [95% CI 0.24–0.9], p = 0.001). When comparing 25 nottreated patients that experienced LFP with 115 that did not, only greater baseline liver fibrosis elastometry values predicted LFP in multivariate analysis (OR 1.84 [95% CI 1.03–3.3], p = 0.03). The best cut-off discriminating for LFP (ROC curve) in not-treated patients was baseline 6.35 kPa (PPV: 80%; NPV: 65%; p < 0.001). Conclusions: In HIV/HCV-coinfected patients with baseline nullmild liver fibrosis (F0–F2), LFP occurred in 18% within a mean of 4.5 years. Fibrosis progression was significantly greater in those with >6.35 kPa, which therefore should also be candidates for new DAA-based therapies. P752 GENETIC POLYMORPHISM IN PNPLA3 GENE IMPACTS DISEASE PROGRESSION AND HEPATOCELLULAR CARCINOMA DEVELOPMENT IN CHRONIC HEPATITIS C M. Kurosaki, K. Tsuchiya, Y. Yasui, N. Tamaki, S. Matsuda, K. Hattori, N. Izumi. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan E-mail: [email protected] Background and Aims: The presence of hepatic steatosis associates with the progression of liver fibrosis and development of hepatocellular carcinoma (HCC) in chronic hepatitis C. Genome wide association studies have revealed that genetic polymorphism in patatin-like phospholipase family 3 protein (PNPLA3) gene is linked to susceptibility to non-alcoholic fatty liver, and some report that PNPLA3 genotype may be related to steatosis in chronic hepatitis C. The aim of this study was to investigate the role of the PNPLA3 genetic polymorphism in chronic hepatitis C in terms of steatosis, fibrosis and the development of HCC.
Journal of Hepatology 2014 vol. 60 | S215–S359
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Age (per 5 years) Body mass index (per 2 kg/m2 ) Hepatitis C virus Negative HCV RNA <2.8 log10 IU/ml HCV RNA 2.8–5 log10 IU/ml HCV RNA 5–6 log10 IU/ml HCV RNA >6 log10 IU/ml HIV Negative HIV RNA undetectable HIV RNA 1.6–4.0 log10 IU/ml HIV RNA >4.0 log10 IU/ml Hepatitis B Surface Antigen positive Insulin Resistance (HOMA-IR) HDL cholesterol (mg/dl) LDL cholesterol (mg/dl) Triglycerides (mg/dl) Alcohol dependence None Harmful drinking Hazardous drinking/dependence Steatosis None Mild Moderate
Prevalence (%), Median (IQR)
Prevalence ratio of cirrhosis (95% confidence interval)
40 (34, 45) 20 (18, 23)
1.18 (1.06, 1.31)* 1.11 (1.03, 1.21)*
383 (56) 65 (10) 12 (2) 48 (7) 174 (26)
1 2.01 (1.09, 3.69)* 1.92 (0.68, 5.40) 3.89 (2.34, 6.49)* 4.26 (2.74, 6.61)*
560 (81) 33 (5) 35 (5) 62 (9) 58 (8) 1.23 (0.55, 2.44) 40 (32, 53) 98 (76, 123) 90 (67, 128)
1 0.44 (0.11, 1.77) 0.75 (0.34, 1.67) 1.10 (0.65, 1.87) 2.12 (1.23, 3.65)* 1.06 (1.02, 1.10)*
144 (21) 86 (12) 466 (67)
1 1.33 (0.69, 2.55) 1.68 (1.03, 2.74)*
341 (49) 290 (42) 58 (8)
1 1.30 (0.91, 1.87) 2.60 (1.54, 4.39)*
*Statistically significant.
Conclusions: In this Indian cohort, beyond HCV, liver fibrosis was driven by alcohol use and metabolic parameters including IR and steatosis. As advances in HCV treatment continue, efforts need to expand access in LMICs and need to consider the increased prevalence of IR and steatosis which may impact disease progression and treatment response. P750 SPONTANEOUS HCV CLEARANCE IN HIV PATIENTS WITH CHRONIC HEPATITIS C BEARING FAVORABLE IL28B ALLELES ON ANTIRETROVIRAL THERAPY E. Vispo, P. Barreiro, J.V. Fernandez-Montero, P. Labarga, C. de Mendoza, A. Trevino, ˜ V. Soriano. Infectious Diseases, Hospital Carlos III, Madrid, Spain E-mail: [email protected] Background and Aims: A quarter of individuals acutely infected with HCV clear the virus spontaneously. Female gender, symptomatic acute hepatitis and IL28B-CC alleles predict a selflimited course. Once chronic HCV infection is established, viral elimination can only be achieved using specific antiviral therapy. Herein, we report a group of chronically HIV–HCV coinfected patients that cleared HCV spontaneously while receiving only antiretrovirals. Methods: Retrospective analysis of all HIV+ individuals with positive HCV-antibodies (HCV-Ab) and negative serum HCV-RNA attended during year 2012 at a reference HIV clinic in Madrid. Results: From a total of 2366 HIV+ individuals, 618 (26%) were HCV-Ab+, of whom 387 (62%) were also positive for serum HCV-RNA. Individuals HCV-Ab+/HCV-RNA-negative were grouped into two categories, those that had eliminated the virus following a course of antiviral treatment (n = 198; 86%) and those who had cleared the virus spontaneously (n = 33; 14%). Eight of the latter were positive for HBsAg and might have cleared HCV as result of
viral interference. However, 6 (24%) out of the remaining 25 did so after being positive for serum HCV-RNA >6 months (median 3.6 years, range 16–120 months). All harbored IL28B-CC alleles and had undetectable plasma HIV-RNA on HAART around the time of HCV clearance. Conclusions: Spontaneous HCV clearance may occur in a subset of chronically HIV/HCV-coinfected patients harboring IL28B-CC whereas being on HAART. Given that antiretrovirals do not display any direct anti-HCV activity, recovery of innate immune responses could be responsible for these late HCV clearance episodes. Thus, periodic testing of serum HCV-RNA is warranted in chronically HIV/HCV-coinfected patients on HAART. P751 DISTINCT VALUES OF LIVER STIFFNESS PREDICT PROGRESSION TO ADVANCED LIVER FIBROSIS IN HIV-INFECTED PATIENTS WITH CHRONIC HEPATITIS C P. Labarga, J.V. Fernandez-Montero, P. Barreiro, M.E. Vispo, R. Sierra, I. Perez, C. de Mendoza, V. Soriano. Hospital Carlos III, Madrid, Spain E-mail: [email protected] Background and Aims: The use of DAA is restricted by some governments to patients with advanced liver fibrosis in order to save costs. However, response rates are lower in patients with advanced liver fibrosis. Methods: All HCV/HIV-confected patients with Metavir F0–F2 (liver stiffness <9.6 kPa by elastometry), and with a follow-up >3 years were identified at our institution. Liver fibrosis progression (LFP) was defined as a change to Metavir F3–F4 estimates. Results: A total of 344 HIV/HCV-coinfected patients with baseline F0–F2 were identified. Hepatitis C therapy was given to 205, of whom 94 (44.8%) achieved SVR. Significant differences between groups included a lower proportion of genotypes 1–4 vs 2–3 (52% vs 90% p < 0.001) and higher IL28B-CC vs non-CC (63% vs 25%, p < 0.001) among SVR patients. After 53 months mean followup, LFP occurred in 5.4% SVR, 25.7% non-SVR and 18% nottreated patients (p = 0.005 SVR vs others). In multivariate analysis, only achievement of SVR independently prevented from LFP (OR 0.47 [95% CI 0.24–0.9], p = 0.001). When comparing 25 nottreated patients that experienced LFP with 115 that did not, only greater baseline liver fibrosis elastometry values predicted LFP in multivariate analysis (OR 1.84 [95% CI 1.03–3.3], p = 0.03). The best cut-off discriminating for LFP (ROC curve) in not-treated patients was baseline 6.35 kPa (PPV: 80%; NPV: 65%; p < 0.001). Conclusions: In HIV/HCV-coinfected patients with baseline nullmild liver fibrosis (F0–F2), LFP occurred in 18% within a mean of 4.5 years. Fibrosis progression was significantly greater in those with >6.35 kPa, which therefore should also be candidates for new DAA-based therapies. P752 GENETIC POLYMORPHISM IN PNPLA3 GENE IMPACTS DISEASE PROGRESSION AND HEPATOCELLULAR CARCINOMA DEVELOPMENT IN CHRONIC HEPATITIS C M. Kurosaki, K. Tsuchiya, Y. Yasui, N. Tamaki, S. Matsuda, K. Hattori, N. Izumi. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan E-mail: [email protected] Background and Aims: The presence of hepatic steatosis associates with the progression of liver fibrosis and development of hepatocellular carcinoma (HCC) in chronic hepatitis C. Genome wide association studies have revealed that genetic polymorphism in patatin-like phospholipase family 3 protein (PNPLA3) gene is linked to susceptibility to non-alcoholic fatty liver, and some report that PNPLA3 genotype may be related to steatosis in chronic hepatitis C. The aim of this study was to investigate the role of the PNPLA3 genetic polymorphism in chronic hepatitis C in terms of steatosis, fibrosis and the development of HCC.
Journal of Hepatology 2014 vol. 60 | S215–S359
S321